This invention relates to novel atrial peptides having useful natriuretic activity.
It is known that the cells of the atrial myocardium in mammals contain numerous membrane-bound storage granules. These characteristic secretory granules, which have been observed in the rat, dog, cat and human atria, resemble those which are in peptide-hormonal producing cells. See DeBold et al., J. Histochem. Cytochem. 26, 1094-1102 (1978). It has been reported that crude tissue extracts of atrial myocardium when injected intravenously into non-diuretic rats produced a rapid and potent natriuretic response. See DeBold et al., Life Sciences 28, 89-94 (1981). Partial purification of rat atrial homogenates with a brief boiling step and fractionation on Sephadex.RTM. was achieved by Trippodo et al., Proc. Soc. Exp. Biol. Med. 170, 502-508 (1982). Natriuretic activity was found by these investigators in the overall molecular weight range of 3600 to 44,000 daltons and in peptide fractions of both the higher molecular weight range of 36,000-44,000 daltons and a lower molecular weight range of 3600-5500 daltons.
In a more recent publication, DeBold et al., Fed. Proc. 42(3), Abstract 1870, page 611 (1983), report the purification of an atrial natriuretic peptide having a molecular weight of 5150 daltons and a sequence of 47 amino acids which the investigators designated "Cardionatrin I". Three additional peaks with natriuretic activity were obtained by high performance liquid chromatography (HPLC) procedures.
In a still later publication, Grammer et al., Biochem. Biophys Res. Commun. 116(2), 696-703, Oct. 31, 1983, disclose the partial purification of a rat atrial natriuretic factor having a molecular weight of approximately 3800 and containing 36 amino acid residues.
Rat atrial extracts also have been fractionated into low molecular weight fractions (&lt;10,000 daltons) and high molecular weight fractions (20,000-30,000 daltons) both of which in vitro relaxed smooth muscle and were potent natriuretic agents when administered intravenously to rats. See Currie et al., Science 221, 71-73 (1983).